1. Field of Invention
This invention relates generally to devices adapted to test the carbon monoxide diffusing capacity (DLco) of the lungs of a human subject to determine the functional integrity of his alveolar-capillary membrane, and more particularly to a phantom assembly which simulates a human subject performing a standard DLco test and which yields a reproducible value for the DLco result, thereby making it possible to verify the accuracy of a standard DLco measuring device.
2. Status of Prior Art
The gas transfer factor for carbon monoxide (CO) is generally referred to as the pulmonary diffusing capacity (DLco). This parameter is commonly used to evaluate the transfer of gas from the distal air space into the pulmonary capillaries. The main reason why this measurement is useful in medical diagnosis is that it is the only non-invasive technique for determining the integrity of the alveolar-capillary membrane.
DLco measurement makes it possible to differentiate pathological entities that differ in the damage they inflict on the lung parenchyma, such as the reduction in alveolar-capillary surface area encountered in emphysema and changes in the permeability of the alveolar-capillary membrane as seen with diffuse interstitial processes (e.g., sarcoidosis, diffuse interstitial fibroses, and many other diseases). It is also important to understand the relationship of hemoglobin concentration and DLco in order to avoid misinterpreting a low DLco which is solely attributable to severe anemia as secondary to a non-existent lung disease.
The following references deal with the pulmonary diffusing capacity of human subjects and disclose known DLco test devices for measuring this parameter as well as clinical applications for this measurement.
1. Bates DV, Macklem PT, Christie RV; Respiratory Function in Disease, Philadelphia, WB Saunders Co., 1971, pp 93-94.
2. Forster, RE, Roughton FJW, Cander L, et al.: Apparent pulmonary diffusing capacity for CO at varying alveolar O.sub.2 tensions. J. Appl Physiol 11:227-289, 1957.
3. Krumholz RA: Pulmonary membrane diffusing capacity and pulmonary capillary blood volume: An appraisal of their clinical usefulness. Am Rev Respir Dis 94:195-200, 1966.
4. Forster RE, Cohn JE, Briscoe WA, et al.: A modification of the Krogh carbon monoxide breath holding technique for estimating the diffusing capacity of the lung: A comparison with three other methods. J Clin Invest 34:1417-1426 1955.
5. Morton JW, Ostensoe LG: A critical review of the single breath method of measuring the diffusing capacity of the lungs. Dis Chest 48:44-54, 1965.
6. Cadigan JB, Marks A, Ellicott MF, et al.: An analysis of factors affecting the measurement of pulmonary diffusing capacity by the single breath method J Clin Invest 40:1495-1514, 1961.
7. Crapo RO, Morris AH: Standardized single breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 123:185-189, 1981.
8. Miller, A, Thornton J. C., Warshau, R, et al., single breath diffusing capacity in a representative sample of the population of Michigan. Am. Rev. Respir. Dis. 127: 270-277, 1983.
Diffusing capacity is normally measured with CO, for this gas has a high affinity for hemoglobin and is normally absent in mixed venous blood. Carbon monoxide has a membrane diffusion coefficient and a rate of reaction with hemoglobin similar to oxygen and linearly related thereto. Since carbon monoxide is normally not found in blood in appreciable amounts, this facilitates the calculation of CO uptake. And because the affinity of hemoglobin for CO is hundreds of times greater than for oxygen, a partial pressure of oxygen that remains in the physiological range is not a significant interfering factor.
The concern of the present invention is with standard devices adapted to carry out DLco measurement by the single-breath technique. In this technique, the human subject or patient who is connected to a spirometer is instructed to inhale a maximum breath (vital capacity), this inhalation starting from the end of a maximal exhalation at residual volume. In inhalation, the patient coupled to the spirometer draws into his lungs a gas mixture of soluble CO (or some other soluble gas, such as acetylene) and a non-soluble, inert tracer gas, usually neon or helium, in a predetermined ratio. The patient then holds his breath for a given number of seconds, usually 10 seconds, this being the breath holding interval or breath holding time (BHT).
When the gas mixture is inhaled by the patient, the non-soluble gas (neon or helium) will be diluted by the residual volume of air remaining at all times in the lungs, whereas the soluble gas (CO), after being diluted as the non-soluble gas and after it has diffused in the circulatory system, will be carried out of the lungs by blood flow owing to its solubility in plasma and by reason of the binding of CO to hemoglobin. The other gases present in the patient (nitrogen and oxygen) will run their usual course through the lungs as during a normal breathing process.
At the completion of the breath holding interval, the patient then proceeds to exhale into the DLco device which acts to collect an alveolar sample to be analyzed for CO concentration and inert gas concentration. The CO uptake during the holding interval can then be calculated from the inspired and expired CO concentrations and the inspired and expired inert gas concentrations. The decrease in CO concentration during the holding interval is exponential in time because the disappearance rate of CO is proportional to the concentration gradient, and this is continuously changing.
Thus a standard DLco measuring device includes means for delivery to a patient, by way of a flow pipe terminating in a mouthpiece, a gas mixture having a predetermined gas concentration of CO relative to that of an inert gas, and means for collecting and evaluating the gas exhaled by the patient into the device through the same mouthpiece.
Accurate calibration of a CO analyzer is of the utmost importance, for if the DLco device is inaccurate, then the DLco reading obtained from a given patient may be misleading and result in an improper diagnosis of his condition. Most CO analyzers are alinear in response and require multiple-point calibration. And because the degree of alinearity is subject to changes with time, full scale recalibration must be repeated on a regular basis.
When, however, a DLco device is installed in a hospital laboratory or other medical diagnostic facility, laboratory personnel who operate the device are not in a position to carry out calibration procedures and must assume that the device is accurate. Yet while this assumption may be false, heretofore the operator of the device has had no means available by which he could verify the accuracy of the DLco instrumention to be sure that test results were produced that could be relied on by the medical diagnostician.
In practice, errors may be introduced into the clinical evaluation of DLco by gas leaks in the DLco device, by faulty gas analyzers, incorrect volume measurements and improper calculation of the DLco from the data yield by the DLco device. Even with multi-point calibrations of each gas analyzer, a technically difficult procedure, and with leak checking of all gas conduits as well as verification of the accuracy of the volume measurement components, the operator of the DLco device has no means available to him to determine directly whether the DLco device is malfunctioning.